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828  structures 1385  species 0  interactions 12749  sequences 927  architectures

Family: PARP (PF00644)

Summary: Poly(ADP-ribose) polymerase catalytic domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Poly(ADP-ribose) polymerase catalytic domain Provide feedback

Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The carboxyl-terminal region is the most highly conserved region of the protein. Experiments have shown that a carboxyl 40 kDa fragment is still catalytically active [2].

Literature references

  1. Ruf A, Mennissier de Murcia J, de Murcia G, Schulz GE; , Proc Natl Acad Sci U S A 1996;93:7481-7485.: Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken. PUBMED:8755499 EPMC:8755499

  2. Simonin F, Hofferer L, Panzeter PL, Muller S, de Murcia G, Althaus FR; , J Biol Chem 1993;268:13454-13461.: The carboxyl-terminal domain of human poly(ADP-ribose) polymerase. Overproduction in Escherichia coli, large scale purification, and characterization. PUBMED:8390463 EPMC:8390463

  3. Ruf A, de Murcia G, Schulz GE; , Biochemistry 1998;37:3893-3900.: Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. PUBMED:9521710 EPMC:9521710


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR012317

Poly(ADP-ribose) polymerases (PARP) are a family of enzymes present in eukaryotes, which catalyze the poly(ADP-ribosyl)ation of a limited number of proteins involved in chromatin architecture, DNA repair, or in DNA metabolism, including PARP itself. PARP, also known as poly(ADP-ribose) synthetase and poly(ADP-ribose) transferase, transfers the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD), to carboxylate groups of aspartic and glutamic residues. Whereas some PARPs might function in genome protection, others appear to play different roles in the cell, including telomere replication and cellular transport. PARP-1 is a multifunctional enzyme. The polypeptide has a highly conserved modular organisation consisting of an N-terminal DNA-binding domain, a central regulating segment, and a C-terminal or F region accommodating the catalytic centre. The F region is composed of two parts: a purely alpha-helical N- terminal domain (alpha-hd), and the mixed alpha/beta C-terminal catalytic domain bearing the putative NAD binding site. Although proteins of the PARP family are related through their PARP catalytic domain, they do not resemble each other outside of that region, but rather, they contain unique domains that distinguish them from each other and hint at their discrete functions. Domains with which the PARP catalytic domain is found associated include zinc fingers, SAP, ankyrin, BRCT, Macro, SAM, WWE and UIM domains [ PUBMED:8016868 , PUBMED:15273990 , PUBMED:15561303 ].

The alpha-hd domain is about 130 amino acids in length and consists of an up-up-down-up-down-down motif of helices. It is thought to relay the activation signal issued on binding to damaged DNA [ PUBMED:8755499 , PUBMED:14739238 ]. The PARP catalytic domain is about 230 residues in length. Its core consists of a five-stranded antiparallel beta-sheet and four-stranded mixed beta-sheet. The two sheets are consecutive and are connected via a single pair of hydrogen bonds between two strands that run at an angle of 90 degrees. These central beta-sheets are surrounded by five alpha-helices, three 3(10)-helices, and by a three- and a two-stranded beta-sheet in a 37-residue excursion between two central beta-strands [ PUBMED:8755499 , PUBMED:14739238 ]. The active site, known as the 'PARP signature' is formed by a block of 50 amino acids that is strictly conserved among the vertebrates and highly conserved among all species. The 'PARP signature' is characteristic of all PARP protein family members. It is formed by a segment of conserved amino acid residues formed by a beta-sheet, an alpha-helix, a 3(10)-helix, a beta-sheet, and an alpha-helix [ PUBMED:15561303 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan ADP-ribosyl (CL0084), which has the following description:

The members of this clan all represent ADP-ribosylating catalytic domains. The structurally conserved regions are located at the NAD binding region [1]. According to SCOP, the ADP-ribosylation domain is thought to have an "unusual fold".

The clan contains the following 23 members:

ADPrib_exo_Tox ADPRTs_Tse2 Anthrax-tox_M Arr-ms ART ART-PolyVal AvrPphF-ORF-2 DarT Diphtheria_C Dot_icm_IcmQ DUF2441 DUF3990 DUF952 Enterotoxin_a Exotox-A_cataly NADase_NGA PARP Pertussis_S1 PTS_2-RNA RES RolB_RolC SidE_mART TNT

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(27)
Full
(12749)
Representative proteomes UniProt
(20615)
RP15
(2686)
RP35
(5463)
RP55
(10089)
RP75
(13213)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(27)
Full
(12749)
Representative proteomes UniProt
(20615)
RP15
(2686)
RP35
(5463)
RP55
(10089)
RP75
(13213)
Alignment:
Format:
Order:
Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(27)
Full
(12749)
Representative proteomes UniProt
(20615)
RP15
(2686)
RP35
(5463)
RP55
(10089)
RP75
(13213)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A , Griffiths-Jones SR
Number in seed: 27
Number in full: 12749
Average length of the domain: 169.6 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 21.45 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.7 26.7
Trusted cut-off 26.7 26.7
Noise cut-off 26.6 26.6
Model length: 194
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PARP domain has been found. There are 828 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044SQ63 View 3D Structure Click here
A0A044SZ27 View 3D Structure Click here
A0A044UHL6 View 3D Structure Click here
A0A077ZD56 View 3D Structure Click here
A0A077ZF35 View 3D Structure Click here
A0A096MJR6 View 3D Structure Click here
A0A0A2V0G3 View 3D Structure Click here
A0A0D2GUR7 View 3D Structure Click here
A0A0D2H1R3 View 3D Structure Click here
A0A0D2H7H2 View 3D Structure Click here
A0A0G2JTL9 View 3D Structure Click here
A0A0G2KEG5 View 3D Structure Click here
A0A0G2KFZ1 View 3D Structure Click here
A0A0G2KLA5 View 3D Structure Click here
A0A0G2L4M0 View 3D Structure Click here
A0A0H5S926 View 3D Structure Click here
A0A0K0EBK1 View 3D Structure Click here
A0A0K0J8U1 View 3D Structure Click here
A0A0N4U654 View 3D Structure Click here
A0A0R0EYR1 View 3D Structure Click here
A0A0R0HN12 View 3D Structure Click here
A0A0R4IH74 View 3D Structure Click here
A0A0R4IVH6 View 3D Structure Click here
A0A0R4IYN3 View 3D Structure Click here
A0A175VYE3 View 3D Structure Click here
A0A175WE52 View 3D Structure Click here
A0A1C1CFA7 View 3D Structure Click here
A0A1C1CQ43 View 3D Structure Click here
A0A1D6FI97 View 3D Structure Click here
A0A1D6H9V4 View 3D Structure Click here
A0A1D6QF51 View 3D Structure Click here
A0A1P6BW34 View 3D Structure Click here
A0A2R8Q7X7 View 3D Structure Click here
A0A2R8Q9E4 View 3D Structure Click here
A0A2R8QE39 View 3D Structure Click here
A0A2R8RJ97 View 3D Structure Click here
A0A2R8RUY6 View 3D Structure Click here
A0A3P7DEL1 View 3D Structure Click here
A0A3P7EZQ8 View 3D Structure Click here
A0A3Q0KLG0 View 3D Structure Click here